Hierarchical dynamics in allostery following ATP hydrolysis monitored by single molecule FRET measurements and MD simulations |
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| Authors: | Steffen Wolf Benedikt Sohmen Bjrn Hellenkamp Johann Thurn Gerhard Stock Thorsten Hugel |
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| Institution: | Biomolecular Dynamics, Institute of Physics, University of Freiburg, Freiburg Germany, Fax: +49 761 203 5883, +49 761 203 5913 ; Institute of Physical Chemistry, University of Freiburg, Freiburg Germany, +49 761 203 6192 ; Engineering and Applied Sciences, Columbia University, New York USA.; Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg Germany |
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| Abstract: | We report on a study that combines advanced fluorescence methods with molecular dynamics (MD) simulations to cover timescales from nanoseconds to milliseconds for a large protein. This allows us to delineate how ATP hydrolysis in a protein causes allosteric changes at a distant protein binding site, using the chaperone Hsp90 as test system. The allosteric process occurs via hierarchical dynamics involving timescales from nano- to milliseconds and length scales from Ångstroms to several nanometers. We find that hydrolysis of one ATP is coupled to a conformational change of Arg380, which in turn passes structural information via the large M-domain α-helix to the whole protein. The resulting structural asymmetry in Hsp90 leads to the collapse of a central folding substrate binding site, causing the formation of a novel collapsed state (closed state B) that we characterise structurally. We presume that similar hierarchical mechanisms are fundamental for information transfer induced by ATP hydrolysis through many other proteins.We report on a study that combines advanced fluorescence methods with molecular dynamics simulations to cover timescales from nanoseconds to milliseconds for a large protein, the chaperone Hsp90. |
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